Long COVID as a Tauopathy: Of "Brain Fog" and "Fusogen Storms".

Long COVID, also called post-acute sequelae of SARS-CoV-2, is characterized by a multitude of lingering symptoms, including impaired cognition, that can last for many months. This symptom, often called "brain fog", affects the life quality of numerous individuals, increasing medical complications as well as healthcare expenditures. The etiopathogenesis of SARS-CoV-2-induced cognitive deficit is unclear, but the most likely cause is chronic inflammation maintained by a viral remnant thriving in select body reservoirs. These viral sanctuaries are likely comprised of fused, senescent cells, including microglia and astrocytes, that the pathogen can convert into neurotoxic phenotypes. Moreover, as the enteric nervous system contains neurons and glia, the virus likely lingers in the gastrointestinal tract as well, accounting for the intestinal symptoms of long COVID. Fusogens are proteins that can overcome the repulsive forces between cell membranes, allowing the virus to coalesce with host cells and enter the cytoplasm. In the intracellular compartment, the pathogen hijacks the actin cytoskeleton, fusing host cells with each other and engendering pathological syncytia. Cell-cell fusion enables the virus to infect the healthy neighboring cells. We surmise that syncytia formation drives cognitive impairment by facilitating the "seeding" of hyperphosphorylated Tau, documented in COVID-19. In our previous work, we hypothesized that the SARS-CoV-2 virus induces premature endothelial senescence, increasing the permeability of the intestinal and blood-brain barrier. This enables the migration of gastrointestinal tract microbes and/or their components into the host circulation, eventually reaching the brain where they may induce cognitive dysfunction. For example, translocated lipopolysaccharides or microbial DNA can induce Tau hyperphosphorylation, likely accounting for memory problems. In this perspective article, we examine the pathogenetic mechanisms and potential biomarkers of long COVID, including microbial cell-free DNA, interleukin 22, and phosphorylated Tau, as well as the beneficial effect of transcutaneous vagal nerve stimulation.

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) comprise a group of illnesses marked by memory and behavioral dysfunction that can occur in up to 50% of HIV patients despite adequate treatment with combination antiretroviral drugs. Iron dyshomeostasis exacerbates HIV-1 infection and plays a major role in Alzheimer's disease pathogenesis. In addition, persons living with HIV demonstrate a high prevalence of neurodegenerative disorders, indicating that HAND provides a unique opportunity to study ferroptosis in these conditions. Both HIV and combination antiretroviral drugs increase the risk of ferroptosis by augmenting ferritin autophagy at the lysosomal level. As many viruses and their proteins exit host cells through lysosomal exocytosis, ferroptosis-driving molecules, iron, cathepsin B and calcium may be released from these organelles. Neurons and glial cells are highly susceptible to ferroptosis and neurodegeneration that engenders white and gray matter damage. Moreover, iron-activated microglia can engage in the aberrant elimination of viable neurons and synapses, further contributing to ferroptosis-induced neurodegeneration. In this mini review, we take a closer look at the role of iron in the pathogenesis of HAND and neurodegenerative disorders. In addition, we describe an epigenetic compensatory system, comprised of bromodomain-containing protein 4 (BRD4) and microRNA-29, that may counteract ferroptosis by activating cystine/glutamate antiporter, while lowering ferritin autophagy and iron regulatory protein-2. We also discuss potential interventions for lysosomal fitness, including ferroptosis blockers, lysosomal acidification, and cathepsin B inhibitors to achieve desirable therapeutic effects of ferroptosis-induced neurodegeneration.

PTSD as an Endothelial Disease: Insights From COVID-19.

SARS-CoV-2 virus, the etiologic agent of COVID-19, has affected almost every aspect of human life, precipitating stress-related pathology in vulnerable individuals. As the prevalence rate of posttraumatic stress disorder in pandemic survivors exceeds that of the general and special populations, the virus may predispose to this disorder by directly interfering with the stress-processing pathways. The SARS-CoV-2 interactome has identified several antigens that may disrupt the blood-brain-barrier by inducing premature senescence in many cell types, including the cerebral endothelial cells. This enables the stress molecules, including angiotensin II, endothelin-1 and plasminogen activator inhibitor 1, to aberrantly activate the amygdala, hippocampus, and medial prefrontal cortex, increasing the vulnerability to stress related disorders. This is supported by observing the beneficial effects of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in both posttraumatic stress disorder and SARS-CoV-2 critical illness. In this narrative review, we take a closer look at the virus-host dialog and its impact on the renin-angiotensin system, mitochondrial fitness, and brain-derived neurotrophic factor. We discuss the role of furin cleaving site, the fibrinolytic system, and Sigma-1 receptor in the pathogenesis of psychological trauma. In other words, learning from the virus, clarify the molecular underpinnings of stress related disorders, and design better therapies for these conditions. In this context, we emphasize new potential treatments, including furin and bromodomains inhibitors.

Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis.

Myalgic encephalomyelitis/chronic fatigue syndrome is a serious illness of unknown etiology, characterized by debilitating exhaustion, memory impairment, pain and sleep abnormalities. Viral infections are believed to initiate the pathogenesis of this syndrome although the definite proof remains elusive. With the unfolding of COVID-19 pandemic, the interest in this condition has resurfaced as excessive tiredness, a major complaint of patients infected with the SARS-CoV-2 virus, often lingers for a long time, resulting in disability, and poor life quality. In a previous article, we hypothesized that COVID-19-upregulated angiotensin II triggered premature endothelial cell senescence, disrupting the intestinal and blood brain barriers. Here, we hypothesize further that post-viral sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome, are promoted by the gut microbes or toxin translocation from the gastrointestinal tract into other tissues, including the brain. This model is supported by the SARS-CoV-2 interaction with host proteins and bacterial lipopolysaccharide. Conversely, targeting microbial translocation and cellular senescence may ameliorate the symptoms of this disabling illness.

Effect of Three Half-Squat Protocols on the Tensiomyographic Twitch Response and Tissue Damage of the Rectus Femoris and the Biceps Femoris.

The aim of this study was to analyse the acute effects of a concentric exercise and two different eccentric overload exercises (EOEs) on blood markers of muscle damage (i.e. creatine kinase [CK], lactate dehydrogenase [LDH], myoglobin [Myo], and malondialdehyde [MDA]) and muscle contractile properties. Ten healthy, young (27 ± 1.5 years, 179 ± 6 cm, 78.7 ± 10.8 kg), physically active men (3.5 ± 1.9 h·w-1) randomly performed three training sessions using the following protocols: a half-squat (HS) as a concentric exercise, and exercises using Versapulley (VP) or YoYo isoinertial technology (YIT) as EOEs (4 x 7 repetitions with a 2 min rest interval between sets). Blood samples and tensiomyography measurements were obtained after each training session. Repeated measures analysis of variance (ANOVA) followed by the Tukey test was used to detect differences between the four time points of each variable. The standardized difference or effect size (ES, 90% confidence limit) in the selected variables was calculated using the basal SD. After all exercises, a greater activity of CK, LDH, and concentration of Myo, and MDA were found compared to baseline values (p < 0.05). A substantially greater activity of CK, LDH, and Myo concentration, but not MDA, were found after EOEs when compared to the HS protocol. Substantially lower tensiomyography results in the rectus femoris (RF) were reported, irrespective of the exercise mode performed. Also, no substantial differences were obtained in the biceps femoris (BF) between EOEs and the HS protocol. Time of contraction (Tc) in the RF was possibly to very likely lower in the HS in comparison to EOEs. Additionally, muscular displacement (Dm) in the RF was substantially lower in the HS compared to EOEs. VP produced higher concentrations of damage markers than YIT and concentric exercise did. Furthermore, tensiomyography variables showed similar activation in both exercises, although higher specific fatigue (in the RF) was registered in the traditional HS.

Prevalence of modifiable factors limiting treatment efficacy of poorly controlled asthma patients: EFIMERA observational study.

Several modifiable factors leading to poor asthma control have been described. We aimed to determine the proportion of patients with inadequate treatment, adherence to it, or critical mistakes with inhaler technique, and their impact on asthma control. We conducted a cross-sectional multicenter observational study including asthma patients referred from primary to specialist care for the first time. Data collected were adequate prescription according to guidelines, treatment adherence, and disease control. Of the 1682 patients (age 45 ± 17 years, 64.6% men), 35.9% showed inadequate prescription, 76.8% low adherence, and 17% critical mistakes with inhaler technique, with significantly less critical mistakes among Easyhaler users versus other dry powder inhaler users (10.3 versus 18.4%; p < 0.05). Factors related to bad asthma control were inadequate prescription (OR: 3.65), non-adherence to treatment (OR: 1.8), and inhaler misuse (OR: 3.03). A higher number of risk factors were associated with a higher probability of having badly controlled asthma.

Cambio organizacional e institucional desde las perspectivas teóricas / Organizational and institutional change from theoretical perspectives / Mudança organizacional e institucional a partir de perspectivas teóricas

Resumen Este artículo pretende identificar la relación que existe entre: institucionalismo, cambio y organización, desde una investigación donde primero se abordaron los textos fundacionales de los conceptos indagados, y luego se revisó el estado del arte de artículos incluidos entre otros en SCOPUS y el Web of Science, para presentar el resultado del análisis en forma de tablas y gráficas, abordando para los distintos autores: el foco, la descripción o el aporte. Finalmente, se propone una interacción teórica para el análisis del cambio. El resultado de esta investigación es soporte conceptual para futuras indagaciones. Clasificación JEL: M10.

Abstract This paper aims to identify the relationship between: institutionalism, change and organization, from a research where the fundamental texts of the concepts investigated were first addressed, and then the state of the art of the articles included among others in SCOPUS and the Web of Science was reviewed, to obtain the result of the analysis in the form of tables and graphs, addressing for the different author authors: the focus, the description or the report. Finally a theoretical interaction is proposed for the analysis of change. The result of this investigation is a conceptual support for future inquiries. JEL Classification: M10.

Resumo Este artigo tem como objetivo identificar a relação entre: institucionalismo, mudança e organização, a partir de uma pesquisa em que os textos fundacionais dos conceitos investigados foram abordados pela primeira vez; e, em seguida, revisou-se o estado da arte dos artigos incluídos entre outros no SCOPUS e na Web of Science para apresentar o resultado da análise na forma de tabelas e gráficos, apresentando d i ferentes autores: o foco, a descrição ou a contribuição. Finalmente, propõe-se uma interação teórica para a análise da mudança. O resultado desta pesquisa é o suporte conceitual para futuras investigações. Classificações JEL: M10.

Validity and Reliability of a 10 Hz GPS for Assessing Variable and Mean Running Speed.

Our purpose was to assess the 10 Hz Viper GPS devices' validity and reliability (STATSport) in both instantaneous and mean speed measuring in accelerations and decelerations in straight-line running conditions. Eight amateur team sport players participated in the study, performing firstly 21 x 40 m sprints at submaximal incremental speed, and secondly 21 x 40 m sprints, with the first stage consisting of submaximal incremental speed, and the second stage of subsequent submaximal decreasing speed. Criteria systems used to evaluate the GPS validity were a radar gun for instantaneous speed, and timing-gates for mean speed. Reliability was measured with two GPS devices carried by the same athlete, running 10 x (20 m + 20 m) sprints with a 180º change of direction and a 10 s inter-set rest interval. Results showed an agreement between GPS devices and the criteria systems measuring instantaneous speed (r = 0.98; standardized mean bias (SMB) = -0.07; standard typical error (STE) = 0.22) and mean speed (r = 0.99; SMB = 0.38; STE = 0.17). The reliability study presented a nearly perfect correlation between devices, a trivial SMB and a small STE (r = 0.97; SMB = 0.04; STE = 0.23). 10 Hz GPS devices are an adequate solution to monitor straight-line running speed in acceleration and deceleration conditions, but we would like to draw attention to the small errors and bias detected, such as the speed overestimation compared with timing gates.

Spanish list of potentially inappropriate drugs in the elderly (ES-PIA project).

PURPOSE: In the last decades, different criteria have been developed for detecting inappropriate prescription in older patients. In Spain, translations and adaptations of international lists are available but it would be necessary a national list which could cope with the peculiarities of our health system, existing pharmaceutical market, and prescription habits. We propose in this project the creation of a Spanish potentially inappropriate drugs list which could be applicable in our clinical scenario. METHODS: We use a Delphi method involving 25 experts from different backgrounds (Clinical Pharmacology, Geriatrics, Rational Use of Drugs and Pharmacy, Primary Care and Pharmacoepidemiology, and Pharmacovigilance) that were asked to participate in two-round questionnaires. For analysis, current recommendations of Worth and Pigni were applied, and every statement was classified into one of three groups: strong, moderate, or low agreement. Statements with strong agreement were accepted to be part of the inadequate prescription list. Moderate agreement statements were selected to enter the second questionnaire, and statements with low agreement were further analyzed to determine if it was due to heterogeneity or due to dispersion in the answers. RESULTS: The first questionnaire consisted of 160 proposed sentences, of which 106 reached a high agreement, 32 a moderate agreement, and 22 a low agreement. All sentences proposed in the second questionnaire reached a strong agreement. The total accepted sentences were 138. CONCLUSIONS: We offer a list of inadequate prescription in older patients adapted to the Spanish pharmacopeia and according to the prescription habits in our environment.

Asthma patient satisfaction with different dry powder inhalers.

BACKGROUND: The preferences and opinions of patients are important when choosing the optimal inhaler device for asthma management. We compared patient satisfaction of three dry powder inhalers in patients with moderate to severe asthma. METHODS: We selected a group of patients treated with EasyhalerTM (n = 164) and a second group of patients treated with TurbuhalerTM (n = 100) or DiskusTM (AccuhalerTM) (n = 64) from the register of an observational, multicenter study. Data of patients were paired according to age, gender, and asthma severity. Patient satisfaction with the inhaler type was assessed with the specific 'Feeling of Satisfaction with Inhaler' (FSI-10) questionnaire. RESULTS: Specific satisfaction with inhaler was statistically significantly higher with EasyhalerTM, as well as the percentage of patients with high satisfaction with inhaler. (FSI-10 score ≥43). Scores for EasyhalerTM were also statistically significantly better for individual FSI-10 items such as learning how to use, inhaler preparation, inhaler use, weight and size, and portability. There were no significant differences in asthma control (ACT, Mini-AQLQ) and adherence (TAI global score). CONCLUSIONS: Specific satisfaction with inhaler was higher with EasyhalerTM in a homogeneous population of patients with moderate to severe asthma. However, the relationship between satisfaction with the inhaler and adherence and asthma control deserves more investigation.

Impact of patient satisfaction with his or her inhaler on adherence and asthma control.

Background: Asthma guidelines recommend considering patient preferences for inhaler choice. However, few studies have assessed the impact of patient satisfaction with an inhaler on adherence and health outcomes. Objective: To assess the impact of patient satisfaction with an inhaler on adherence and health outcomes in asthma. Methods: In a cross-sectional, observational, multicenter study, 778 patients with moderate or severe asthma and who were treated with maintenance inhalers completed a number of scales and questionnaires: the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire, the Treatment Satisfaction Questionnaire for Medication, the Test of Adherence to Inhalers (TAI), the Morisky-Green questionnaire, and the Asthma Control Test (ACT). Results: The study population was categorized according to a median FSI-10 score as high (49.4%) and low (50.6%) satisfaction with their inhaler. Logistic regression analysis showed that high specific satisfaction with an inhaler was associated with the younger age group (odds ratio [OR] 0.976 [95% confidence interval {CI} 0.965-0.987]); male gender (OR 1.725 [95% CI 1.187-2.507]); controlled asthma: ACT score ≥ 20 (OR 1.664 [95% CI 1.133-2.445]); high general satisfaction with treatment (OR 4.861 [95% CI 3.335-7.085]); high adherence to inhaler: TAI score ≥ 46 (OR 1.546 [95% CI 1.025-2.332]); nonsevere asthma (OR 1.056 [95% CI 0.648-1.721]); and no trouble with inhaler use (OR 0.401 [95% CI 0.174-0.922]). Conclusion: High patient satisfaction with an inhaler, irrespective of received medication, was related to adherence and asthma control. Our results pointed out the relevance of inhaler choice in inhaled therapy; these results could be useful for designing new strategies targeted to increase adherence in patients with asthma.

Epigenetics of Subcellular Structure Functioning in the Origin of Risk or Resilience to Comorbidity of Neuropsychiatric and Cardiometabolic Disorders.

Mechanisms controlling mitochondrial function, protein folding in the endoplasmic reticulum (ER) and nuclear processes such as telomere length and DNA repair may be subject to epigenetic cues that relate the genomic expression and environmental exposures in early stages of life. They may also be involved in the comorbid appearance of cardiometabolic (CMD) and neuropsychiatric disorders (NPD) during adulthood. Mitochondrial function and protein folding in the endoplasmic reticulum are associated with oxidative stress and elevated intracellular calcium levels and may also underlie the vulnerability for comorbid CMD and NPD. Mitochondria provide key metabolites such as nicotinamide adenine dinucleotide (NAD+), ATP, α-ketoglutarate and acetyl coenzyme A that are required for many transcriptional and epigenetic processes. They are also a source of free radicals. On the other hand, epigenetic markers in nuclear DNA determine mitochondrial biogenesis. The ER is the subcellular organelle in which secretory proteins are folded. Many environmental factors stop the ability of cells to properly fold proteins and modify post-translationally secretory and transmembrane proteins leading to endoplasmic reticulum stress and oxidative stress. ER functioning may be epigenetically determined. Chronic ER stress is emerging as a key contributor to a growing list of human diseases, including CMD and NPD. Telomere loss causes chromosomal fusion, activation of the control of DNA damage-responses, unstable genome and altered stem cell function, which may underlie the comorbidity of CMD and NPD. The length of telomeres is related to oxidative stress and may be epigenetically programmed. Pathways involved in DNA repair may be epigenetically programmed and may contribute to diseases. In this paper, we describe subcellular mechanisms that are determined by epigenetic markers and their possible relation to the development of increased susceptibility to develop CMD and NPD.

Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease.

Corticotrophin releasing factor, vasopressin, oxytocin, natriuretic hormones, angiotensin, neuregulins, some purinergic substances, and some cytokines contribute to the long-term modulation and restructuring of cardiovascular regulation networks and, at the same time, have relevance in situations of comorbid abnormal stress responses. The synthesis, release, and receptor expression of these mediators seem to be under epigenetic control since early stages of life, possibly underlying the comorbidity to coronary artery disease (CAD) and stress-related disorders (SRD). The exposure to environmental conditions, such as stress, during critical periods in early life may cause epigenetic programming modifying the development of pathways that lead to stable and long-lasting alterations in the functioning of these mediators during adulthood, determining the risk of or resilience to CAD and SRD. However, in contrast to genetic information, epigenetic marks may be dynamically altered throughout the lifespan. Therefore, epigenetics may be reprogrammed if the individual accepts the challenge to undertake changes in their lifestyle. Alternatively, epigenetics may remain fixed and/or even be inherited in the next generation. In this paper, we analyze some of the common neuroendocrine functions of these mediators in CAD and SRD and summarize the evidence indicating that they are under early programming to put forward the theoretical hypothesis that the comorbidity of these diseases might be epigenetically programmed and modified over the lifespan of the individual.

Eccentric-Overload Training in Team-Sport Functional Performance: Constant Bilateral Vertical Versus Variable Unilateral Multidirectional Movements.

PURPOSE: To analyze the effects of 2 different eccentric-overload training (EOT) programs, using a rotational conical pulley, on functional performance in team-sport players. A traditional movement paradigm (ie, squat) including several sets of 1 bilateral and vertical movement was compared with a novel paradigm including a different exercise in each set of unilateral and multi-directional movements. METHODS: Forty-eight amateur or semiprofessional team-sport players were randomly assigned to an EOT program including either the same bilateral vertical (CBV, n = 24) movement (squat) or different unilateral multidirectional (VUMD, n = 24) movements. Training programs consisted of 6 sets of 1 exercise (CBV) or 1 set of 6 exercises (VUMD) × 6-10 repetitions with 3 min of passive recovery between sets and exercises, biweekly for 8 wk. Functional-performance assessment included several change-of-direction (COD) tests, a 25-m linear-sprint test, unilateral multidirectional jumping tests (ie, lateral, horizontal, and vertical), and a bilateral vertical-jump test. RESULTS: Within-group analysis showed substantial improvements in all tests in both groups, with VUMD showing more robust adaptations in pooled COD tests and lateral/horizontal jumping, whereas the opposite occurred in CBV respecting linear sprinting and vertical jumping. Between-groups analyses showed substantially better results in lateral jumps (ES = 0.21), left-leg horizontal jump (ES = 0.35), and 10-m COD with right leg (ES = 0.42) in VUMD than in CBV. In contrast, left-leg countermovement jump (ES = 0.26) was possibly better in CBV than in VUMD. CONCLUSIONS: Eight weeks of EOT induced substantial improvements in functional-performance tests, although the force-vector application may play a key role to develop different and specific functional adaptations.

Thermal behaviour of romarchite phase SnO in different atmospheres: a hypothesis about the phase transformation.

A study was conducted on the transformation of SnO to SnO2 using X-ray diffraction and subjecting the SnO to heat treatments between 300 °C < T < 600 °C in two different atmospheres, argon and air. The intermediary oxide that appears in the disproportionation process was identified as Sn2O3. In an argon atmosphere, decomposition occurs in three stages: (1) a direct transformation of SnO to SnO2, (2) the formation of some intermediary Sn2O3 from SnO, and (3) the conversion of the Sn2O3 to SnO2 with the formation of metallic tin, Sn (l). When an atmosphere of air is used, however, a reaction occurs, concurrent with the decomposition reactions, that relates to the specific oxidation of the metallic tin produced in the course of the three process stages.

Esthetic Restoration with Artificial Gingiva in an Atrophied Alveolar Ridge: Clinical Report.

Management of the anterior maxilla is a challenge in compromised clinical situations such as loss of teeth or soft tissues, alveolar ridge defects, or loss of all three. This report shows the systematic sequence of surgical and prosthetic management in a case of Seibert Class III alveolar atrophy where the patient refused a removable prosthesis. This was resolved with a hybrid metal/porcelain prosthesis with 17-degree multiunit abutments, leading to totally satisfactory esthetic and functional results.

Thermographic Assessment of Eccentric Overload Training Within Three Days of a Running Session.

The aim of this study was to analyze the changes in patellar and Achilles tendons between a group trained using eccentric overload and an untrained group within 3 days of a running session. To this end, infrared thermography (IRT) will be used. Twenty healthy male subjects were divided into 2 groups. One group performed a 6-week squat training in the flywheel before the running session. During the running intervention, both groups ran in 3 different days, for 1 hour each, at 80% maximal heart rate. Before, just after, and after 10 minutes of the running intervention, participants were assessed using IRT. Eccentrically trained groups showed a statistically significant difference (analysis of variance, p = 0.0049) expressed as a smaller bilateral increase in temperature in the patellar tendon just before the first running day (right side, 0.11 °C; left side, 0.29 °C). On the other days of running and in the Achilles tendon groups, similar changes were observed: an increase in the temperature after running and no significant difference between contralateral limbs. Our results point at eccentric overload training providing a better adaptation for the first day of running. IRT is an easy-to-apply noninvasive tool to analyze and compare the effects of performance on tendon tissues.

Relajación residual en la unidad de cuidado posanestésico / Residual neuromuscular blockade in the post-anesthesia care unit

El uso de relajantes neuromusculares en la práctica clínica es cada día más frecuente e indispensable en el acto anestésico y la unidad de cuidado intensivo. Aunque los bloqueantes neuromusculares tanto aminoesteroideos como benzilisoquinolinas de última generación tienen efectos adversos mínimos, la relajación residual es una complicación de incidencia considerable asociada con un incremento en la morbilidad y mortalidad. Debido a esto planteamos la importancia de conocer los diferentes métodos de monitoria del bloqueo neuromuscular con su interpretación, haciendo énfasis en la monitoria con el tren de cuatro(TOF), la razón entre la primera y la cuarta respuesta T4/T1 (TOF RATIO) y estrategias de prevención de la relajación residual...

The use of neuromuscular blocking agents in clinical practice is more common every day and is indispensable in anesthesia and in the intensive care unit. Although neuromuscular blocking agents, both the latest generation of aminosteroids as well as benzylisoquinolines, have minimal adverse effects, a significant incidence of residual neuromuscular blockade constitutes a complication associated with increased morbidity and mortality. For this reason we advocate the importance of knowledge on the various neuromuscular block monitoring methods and their interpretation, emphasizing train-of-four (TOF) stimulation, ratio between the first response to the fourth response T4/T1 (TOF RATIO) and prevention strategies of residual neuromuscular blockade...

Efectividad y seguridad de Risperidona comparada con Haloperidol, Olanzapina, Clozapina, Quetiapina, Aripiprazol, Clonidina, Placebo en personas con diagnóstico de trastorno del espectro autista - TEA / Effectiveness and Safety of Risperidone compared to Haloperidol, Olanzapine, Clozapine, Quetiapine, Aripiprazole, Clonidine, Placebo in People with Autism Spectrum Disorder - ASD

Introducción: Los trastornos del espectro autista (TEA) son un grupo de discapacidades del desarrollo, de características crónicas y que afectan de manera distinta a cada paciente. Los TEA se definen como una disfunción neurológica crónica con fuerte base genética que desde edades tempranas se manifiesta en una serie de síntomas basados en la tríada de Wing que incluye: la comunicación, flexibilidad e imaginación e interacción social. No existe tratamiento curativo para el TEA, las terapias están dirigidas al control de los síntomas. Debido a la heterogeneidad de los síntomas, las terapias deben adaptarse al caso individual del paciente. Las intervenciones para los pacientes con diagnóstico de TEA pueden incluir educación, terapia conductual, o manejo farmacológico. Objetivo: realizar una revisión, apreciación crítica y síntesis de la evidencia disponible sobre la efectividad y seguridad de la risperidona para el tratamiento de personas con diagnóstico de trastorno del espectro autista. Metodología: la evaluación fue realizada de acuerdo con un protocolo definido a priori por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, LILACS y Google, sin restricciones de idioma, fecha de publicación y tipo de estudio. Las búsquedas electrónicas fueron hechas en octubre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y una consulta con expertos temáticos. La tamización de referencias se realizó por dos revisores de forma independiente y los desacuerdos fueron resueltos por consenso. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad predefinidos. Las características y hallazgos de los estudios fueron extraídos a partir de las publicaciones originales. Resultados: Se identificó evidencia proveniente de 4 revisiones sistemáticas de moderada y alta calidad, que compraban risperidona con placebo, se encontró que risperidona fue superior a placebo en los desenlaces de impresión global de salud, irritabilidad, hiperactividad, estereotipias. Conclusiones: La risperidona comparada con placebo sugiere efectividad en relación a mejoría de síntomas como irritabilidad, hiperactividad y estereotipias, así como, de la impresión clínica global. No se puede establecer con la evidencia actual el perfil de seguridad de la risperidona, solo se evidenció que los pacientes que reciben risperidona tienen mayor riesgo de aumento de peso y de presentar síndrome de extrapiramidalismo.

Exposición a plaguicidas persistentes y no persistentes en población no expuesta laboralmente de la isla de Tenerife / Exposure to persistent and non-persistent pesticides in a non-occupationally exposed population in Tenerife Island (Spain)

Objetivo: La exposición crónica a plaguicidas no persistentes se ha relacionado con diversas patologías crónicas; sin embargo, pocos estudios han evaluado la exposición a plaguicidas no persistentes en población española. Métodos: En 2007 se determinó la presencia de 24 plaguicidas mediante cromatografía de gases/espectometría de masas en 363 muestras de suero de adultos no laboralmente expuestos de Tenerife. Resultados: El 99,45% presentaron residuos (6 ± 2 plaguicidas/muestra). Los plaguicidas más frecuentes fueron piretroides (96,1%), organofosforados (93,9%) y organoclorados (92,3%). En el 81% de los sujetos se detectaron bifentrina y malatión, considerados neurotóxicos, y en el 50% hexaclorobenceno, DDT y buprofezina. El malatión, un "obesógeno ambiental", se detectó en el 82%, y plaguicidas considerados "disruptores endocrinos" en el 97,2% de las muestras. Conclusiones: Existe una exposición inadvertida a plaguicidas no persistentes que puede afectar a la salud de nuestra población, por lo que se hace necesario incluirlos en los estudios de monitorización (AU)

Objective: Chronic exposure to non-persistent pesticides (NPPs) is of concern because these substances have been associated with chronic diseases. However, few studies have addressed chronic exposure to NPPs in Spanish populations. Methods: We determined the presence of 24 pesticide residues by gas chromatography/mass spectrometry in 363 serum samples obtained from non-occupationally exposed adults from Tenerife island in 2007. Results: Most of the samples (99.45%) showed detectable residues (6 ± 2 pesticides per sample). The most frequently detected pesticides were pyrethrins (96.1%), organophosphates (93.9%) and organochlorines (92.3%). The neurotoxicants bifenthrin and malathion were detected in 81% of the samples and hexachlorobenzene DDT and buprofezin in more than 50%. Malation, an "environmental obesogen", was detected in 82%, and "endocrine disrupter" pesticides were present in 97.2% of the samples. Conclusions: Because there is clear, continuous and inadvertent exposure to NPPs that may be inducing adverse effects on human health, NPPs should be included in biomonitoring studies (AU)